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Intracerebral hemorrhage (ICH) causes long term neurological abnormality or death. Oxidative stress is closely involved in ICH mediated brain damage. Steroid receptor cofactor 3 (SRC-3), a p160 family member, is widely expressed in the brain and regulates transactivation of Nrf2, a key component of antioxidant response. Our study aims to test if SRC-3 is implicated in ICH mediated brain injury. We first examined levels of SRC-3 and oxidative stress in the brain of mice following ICH and analyzed their correlation. Then ICH was induced in wild type (WT) and SRC-3 knock out mice and how SRC-3 deletion affected ICH induced brain damage, oxidative stress and behavioral outcome was assessed. We found that SRC-3 mRNA and protein expression levels were reduced gradually after ICH induction in WT mice along with an increase in oxidative stress levels. Correlation analysis revealed that SRC-3 mRNA levels negatively correlated with oxidative stress. Deletion of SRC-3 further increased ICH induced brain edema, neurological deficit score and oxidative stress and exacerbated ICH induced behavioral abnormality including motor dysfunction and cognitive impairment. Our findings suggest that SRC-3 is involved in ICH induced brain injury, probably through modulation of oxidative stress.
相似文献The expression of IL-2RA and IL-2RB was correlated with breast cancer (BC) progression. However, there is no literature investigating the association of IL-2RA and IL-2RB polymorphisms with BC predisposition among Chinese Han Women. Seven SNPs in IL-2RA and IL-2RB were genotyped by Agena MassARRAY platform among 553 BC patients and 550 healthy controls. Odds ratios (OR) and 95% confidence interval (CI) adjusted for age were calculated for the effect of IL-2RA and IL-2RB variants on BC susceptibility. IL-2RA rs12722498 was a protective factor for BC occurrence (OR?=?0.70, p?=?0.019), especially in subjects with age?≤?52 years (OR?=?0.55, p?=?0.004). IL-2RA rs12569923 (OR?=?9.07, p?=?0.033), IL-2RB rs2281089 (OR?=?0.67, p?=?0.043) and rs9607418 (OR?=?0.59, p?=?0.012) were related to the incidence of estrogen receptor positive (ER?+) BC. IL-2RB rs3218264 (OR?=?1.38, p?=?0.010) and rs9607418 (OR?=?0.56, p?=?0.009) were associated with the risk of developing progesterone receptor positive (PR?+) BC. Rs2281089 (OR?=?1.54, p?=?0.012) and rs1573673 (OR?=?0.72, p?=?0.035) were correlated to Ki-67 level. Moreover, IL-2RB rs2281089 (OR?=?0.72, p?=?0.022) showed a reduced risk of BC metastasis, and IL-2RA rs12722498 (OR?=?0.54, p?=?0.030) had a lower frequency in BC patients with tumor size?>?2 cm. Our study identified the potential effect of genetic variations in IL-2RA and IL-2RB on BC susceptibility and/or BC clinicopathologic indicators among Chinese Han Women.
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